Thursday, August 12, 2010

Unit accelerate neuronal toxicity tests

Unit neurons speed tests racunPara level scientists in Germany have developed an alternative to animal testing for the rapid detection and identification of chemicals that contain a health risk to the nervous system.
Several laboratories worldwide neurotoksinitas affects enormous challenges in screening chemicals for growing catalog which identify the risks to human health, with the introduction of legislation mnegacu - invitation of the scope of the EU. The in vitro toxicity testing has traditionally been done using animals, but with the excess of expenditure relating to the funds and the number of animals, salinity reliable penggujian necessary. The lack of comparable readings between in vivo and in vitro systems can mnyajikan suaatu problems, said Jonathan West at the University of Dortmund, Germany, but West said he had to solve these problems by using neural networks.
This new test platform, called the test networking (NFA), to monitor the connection (or changes), especially between neurons - the neurons are placed and their neighbors. The formation of some of these connections is one of the basic principles in memory and learning, and is often the clinical signs neurotoksinitas gangguannnya, West said. "Because the NFA test the connections of neurons following is an in vitro model is comparable to the in vivo situation," he added.
West to neurons - in the composition of human neurons segilima using patterns of cells - and then, easy to control the formation of networks. Composition becomes acrylamida exposure, a neurotoxin that blocks the reference compounds and networking to distinguish between the effects of neurotoxins with cytiotoksin. Without the need to place neurons - neurons or measure the length of connections, this means that a typical arrangement should only take three hours, compared with more than 200 hours of manual testing.
"Application of micro system simple and sophisticated - this engineering can significantly improve the biological standard protocol," says Marco Cecchini, an expert on high-level bio pemolaan resolution, the National Enterprise for Nanoscience and Nanotechnology, Pisa, Italy.
"NFA also apply in the context of reproductive testing of toxin levels are expected mngkonsumsi approximately 60% of all animals requires outreach and other areas necessary for the new assay in vitro 'addition of Marcel Leist University of Konstanz, Germany, who worked on this project with the West.
Today, the team is working with teams across Europe to adopt the NFA in use with a network of neural cells, but 'real litmus test digunakankah NFA or not taken by the laboratory neurotoksikologi and accepted by the authorities, "said West.

A coat of cunning Ebola virus

The cunning virus structural layer EbolaBiologi: Protein that hides the viral RNA to avoid immune system detection of a deadly virus
Carmen Drahl
Ebola, RNA, VP35
X-ray structure of the two copies of the Ebola virus in Zaire protein (green, blue) to strengthen the viral RNA (pink).
A new molecular view of how the veil lifted Ebola virus not recognized by the immune system: a mechanism is used to disguise signs pemantelan penginvasiannya gossipy (Structural Nat. Mol. Biol., Doi: 10.1038/nsmb 1765). These findings may lead to the cure of Ebola hemorrhagic fever, a dangerous and often fatal disease that is accompanied by a viral infection.
Ebola is an agent of transmission of a beating where there is no cure, clear style K. Amarasinghe, a biochemist at Iowa State University The virus has left the identity card in some cells during infection: a double-stranded RNA - yours. Generally, these RNAs can activate the human immune system. However, this virus produces a protein called VP35 which makes RNA, then compared the immune response.
To learn more about how the camouflage, Amarasinghe, a virologist Christopher F. Basler of Mount Sinai School of Medicine, and colleagues to determine the X-ray crystal structure of double-stranded RNA binds to the VP35 Ebola virus in Zaire species are deadly. They found that a variety of coats assemble copies of VP35 RNA. A copy of hydrophobic amino acids using a cord bag mngenali double RNA strands of RNA and the back cover. Copies ynag column binding others through a point of basic amino acids. The changes in two basic residues is sufficient to destroy the disease causing ability of the virus in guinea pigs, the team found a new - this new (J. Virol., Doi: 10.1128/JVI.02459-09) .
In the past month, a team led by structural biologist Erica Ollman Saphire Scripps Research Institute detect VP35 RNA binding itself unusual in a few species of pathogenic Ebola (Proc. Natl. POLICY. Science. U.S. , doi: 10.1073/pnas 0.0910547107). This gives the satisfaction that strukturdari different species, obtained under different conditions showed the same unorthodox mechanism, Ollman Saphire said. "Of course, if you look at an unusual virus, you're bound to find something unusual," he said.
Besides studying how viruses work, the team hopes that the structural point of view is filled with a small molecule drug discovery efforts of the disease, which is the end - the end of this behind the development of vaccines, says Basler .

Sweeten the mixture of bacterial synthesis of biomedicine

The bacteria in the human stomach is called to be a good plant for biological drugs and thanks to modify some of the genes of other species, causing gastroenteritis. Using a pair that sounds unlikely, researchers Ammrika States and Switzerland have created the first bacterial methods to take full advantage of the glycoprotein found in the human body. This approach provides unprecedented sebelumnyaterhadap sugar control was recorded in protein and can further improve the performance of biological medicines.
"This method is a combination dapa provide an efficient way to produce glycoprotein home remedies, such as monoclonal antibodies," clearly Lai-Xi Wang from the University of Maryland, USA. As a glycoprotein, the monoclonal antiobodi ongoing activities may be inconsistent due to the polysaccharide glycan - or - that produce much. "Glycoprotein produced as a live mix," said Wang "Only a few of the glycoform that is very active." Glycosylating a homogeneous protein with an active glycan produce a more potent drug.
Escherichia coli is usually harmless, where they can destroy microbes have been used in industry to produce proteins, but the glycoprotein, where they can add the sugar memodulasikan. "In general, bacteria do not have proteins glycosylasi team," said Wang But once Mark Aebi, Swiss Federal Institute of Technology (ETH) in Zurich has found that the bacteria Campylobacter jejuni is dangerous not to have an unusual ability to paste sugar to proteins. Engineering and transfer equipment C. jejuni in E. glycosylasi coli and then used an enzyme to modify one part sugar to produce the protein was uniformly glycosylasi
Unfortunately, C. Jejuni glycoprotein produced normally trigger an immune response in the human body. This is because bacteria N-glucan, an alpha-linked oligosaccharides N-acetyl-galactosamine, which is attached to asparagine residues of proteins through bacillosamine aminosugar an unusual appeal that makes it not as glycan in humans. Aebi and Wang are the computer before transferring genes in E. glycosylasi coli, to change the sugar is first attached to asparagine in N-acetylglucosamine that is commonly found in our bodies. Then, using enzymatic methods in vitro, which decorate and replace residues of N-acetyl-galactosamine to the N-glycans that glycosylasi selected for "human" homogeneous.
"The ability to express proteins in E. coli is easier and cheaper," says Antonio Fairbanks, University of Canterbury, New Zealand. How to Fairbanks, who founded the company in the UK targeting drugs, Glycoform, said that while this method worked with glycoprotein C. jejuni had glycosylasi IgG antibodies in humans are generally a bit incomplete.

The risk of cancer of the "third hand smoke '

Researchers at the risk of cancer from the "third hand smoke 'in the United States found that nicotine residue on the outside can react with a little ambient gas to produce compounds that cause cancer. This research is expected to give a new hopeful about the potential dangers of 'third hand smoke' - where snuff smoke toxins can be left burning on the surface of household appliances.
"Special compounds - such as ambient nitrous acid, nitrogen dioxide or ozone - is featured in a lot of free air that was in the room," said Hugo Destaillats, who led the research at Lawrence Berkeley National Laboratory in California , USA. This is because that is generated by burning gas supplies outside the room where the fire or the use of electronic equipment.
Destaillats and equipment they use cellulose as a model foreign material, and place a barrier inside a smoker truck for three days. Then analyzes these barriers and compare the results of laboratory tests on the basis of cellulose-based were exposed to nicotine evaporates in a tubular flow reactor. "We found that some of the [ambient gas in the] truck to react with residual nicotine to produce snuff-specific nitrosamines, known carcinogens."
Two of these compounds - N-nitroso nornicotine (NNN) and 4 - (methylnitrosamino) -1 - (3-pyridyl)-1-butanone (NNK) is also found in the smoke of snuff, as has been well studied in the past. However, a third compound was identified that is not unusual in the smoke of snuff: 1 - (N-methyl-N-nitrosamine) -1 - (3-pyridinyl)-4-butyraldehyde), called nna. Because of this there was no smoke, nna not been investigated in detail, but this team of experts toksikologist now hope that this will some studies.
Unlike second-hand cigarette unconsciously breathe in public areas, the dangers of secondhand smoke is not clear roots. There are many factors involved, from the size and ventilation of the outdoor environment of the materials used berbedayang - mikrolayer of the toxin can accumulate lint, wallpaper, clothing and hair.
"One of the specific risk groups such smoke are children," said Jonathan Winickoff, a pediatrician who has studied teacher attending the dangers of cigarettes a third hand of the Harvard Medical School. «Children interact with their environment in ways that are very different, so their exposure can be 20 times higher than in adults."
"I think this is important work that will create scenarios for a study on residual contamination of snuff smoke," said Winickoff. "The consequences of third-hand smoke is the absence of a way for someone to smoke outside the room without pollute the environment. "

DNA molecular midwife helped deliver

short strands of DNA as siklusisasi (above), but the existence of the molecule interkalator (green) form a long chain polymerik
U.S. investigators have revealed new clues about how the earliest life forms have been arranged in the primordial soup. The secret is the possibility of "molecular midwife" - compounds that play a crucial role in the combination of small nucleotide fragments in a first polymeric material genetically.
"There are so many unanswered questions about how the genetic polymer formed in the prebiotic Earth's age - ie without the presence of enzyme proteins that exist today," said Nicholas Hud, who led the research at the Institute of Technology Georgia. "We are investigating how a small nucleotide fragment could join a long polymer - DNA or RNA strands to form the beginning."
One problem in investigating how DNA begins to form a small chain of nucleotides - from three to four bases long - flexible enough to bind. Also they like and tend to bond mengriting intramolekular and circular, forming a small ring of the chain length.
Today, Hudson's team has found that the presence of certain compounds can menstabilakan development of DNA strands. Compounds known as interkalator - large, flat molecules that can slide between the bases in DNA as a plank of wood - by holding the structure in place by non-covalent interactions. These compounds are called by the name of molecular midwife for this team, because this polymer is sometimes no longer needed.
Two examples of these are midwives Ethidium Coralynes - multicincin general organic compounds, but unlike these two compounds is the first time a midwife. "Our work suggests that the possible existence of flat molecules midwives who participated in the beginning of life on Earth," says Hood. "But this is still not identified and may be there too."
An interesting perspective is the first molecular midwife is responsible for selecting a combination of base paangan adenine-thymine (AT) and cytosine-guanine (CG) DNA does. As can stabilize ethidium diteemukan Watson-Crick pairs traditional aza3 azacyanine found to stabilize an alternative system in which binding of adenine adenine (AA).
"Midwives different molecular can be selective in the installation of the system is fundamentally different," says Hood. "Our hypothesis is that the original molecule midwives help choosing a partner base that is used in the DNA."
"This study shows a very good thing at all that a combination of nucleic acid molecules that are structurally independent seem to produce systems that can replicate - and later in life - from the nucleic acid itself," said Clemens Richert, expert DNA at the University of Stuttgart, Germany.